The long-range objective of research outlined in this proposal is to delineate mechanisms essential for a clear understanding of the biochemical correlates of alcoholism. Biosynthetic processes responsible for the adaptive increase in ethanol and oxygen uptake in perfused livers of normal and ethanol-treated rats will be studied in detail. Moreover, mechanisms responsible for the development of tolerance and physical dependence to alcohol in the central nervous system will be probed. The role of cyclic nucleotides in these processes will be studied exhaustively. The role of genetics in alcoholism will be examined by identifying which hepatic and central nervous system components involved in drunkenness are hereditable. These experiments will be followed by the development of an animal model for alcoholism taking important genetic components related to drunkenness into account. After exhaustive studies of the hepatic metabolic and central nervous system responses to ethanol of this new model, biological determinants of alcoholism will be identified which will serve as the basis for a simple screening test for the identification of prealcoholics.